1. Field of the Invention
The present invention relates to an apparatus and method for performing measurement of information associated with an absorptive constituent in a scattering medium such as a living body by utilizing light and, more particularly, to an apparatus for measuring absorption information in the scattering medium, capable of measuring the concentration of a specific absorptive constituent in the scattering medium, its time change, its spatial distribution, and the like, and improving measurement precision.
2. Related Background Art
Measurement or imaging in a living body using light is advantageously non-invasive and allows analysis of internal components using a spectrum as an optical characteristic inherent to a given material. However, a living body is a typical scattering medium, and light is scattered and/or absorbed at random inside the living body. Excellent measurement and imaging as in X-ray or ultrasonic CT cannot be performed. That is, as most of the light components are greatly scattered inside the living body, straight light components are rarely present.
There are several reports and attempts in measurement and imaging of a scattering medium such as a living body using light. Main prior arts will be represented as references.sup.1-12) at the end of this part (the number of each reference will be referred to with .sup.X) hereinafter). Of these references, references.sup.1-3) describe detection of straight light in a very small amount from scattered light. This detection has very poor light utilization because the amount of straight light is very small. In addition, measurement and imaging are time-consuming. This method is impossible to measure a large object such as a head. This method is not suitable for quantitative measurement of the concentration of absorptive constituents widespread in the living body and the concentration and absorption coefficients of localized absorptive constituents, although this quantitative measurement is one of the objects of the present invention.
Various kinds of references.sup.4-11) utilizing scattered light are available. The reference.sup.4) proposed by Delpy et al. describes image reconstruction such that scattered light outputs obtained upon incidence of pulsed light are detected at a plurality of positions, and an image representing internal absorptive constituents or an absorption distribution is reconstructed from these data. This method of image reconstruction is similar to that in X-ray CT. However, an image reconstruction algorithm for the scattered light is very complicated and is incomplete. A practical finding is not obtained yet.
Tamura et al..sup.5) propose a principle of an oxyhemoglobin concentration and a reduced or deoxygenated hemoglobin concentration in accordance with a change of absorbance optical density with respect to incident light components having three different wavelengths. Optical CT construction using this principle is also attempted. However, this method poses a lot of problems in terms of measurement precision because the length of an optical path upon a change in absorption coefficient is assumed to be constant. This problem is common to subsequent prior art methods and will also be described later.
References.sup.6-8) are attempts for measuring internal absorption information by analyzing the time-resolved response upon the incidence of pulsed light to the medium. An output light signal upon incidence of the pulsed light on a scattering medium is temporally broadened by scattering and absorption constituents and has a long decay tail. Patterson et al.sup.6) assume a model of uniform scattering medium to analytically obtain the light signal output. A waveform representing a time change in intensity of the optical output signal given by the formula defined by Patterson et al. matches a waveform obtained by an experiment using a scattering medium (e.g., a uniform medium) having a simple structure. According to Patterson et al., the absorption coefficient of absorptive constituents in the scattering medium is given by an incline (differential coefficient) obtained when the optical signal is sufficiently attenuated, i.e., when a sufficiently long period has elapsed. According to this method, however, since the optical signal corresponding to a portion subjected to absorption coefficient measurement must be sufficiently attenuated, the S/N ratio of the signal becomes low, and an error increases. Therefore it is difficult to use this method in practice. In addition, a long period of time must elapse until the optical signal is sufficiently attenuated, and the measurement time is inevitably prolonged.
To the contrary, Chance et al. propose a method.sup.7) of obtaining an incline at an earlier timing and approximating an absorption coefficient with the incline value when the light intensity is not sufficiently attenuated. According to their proposal, an error in a simple scattering medium such as a uniform medium is about 10%. However, there is no guarantee to monotonously attenuate the above waveform in an actual living body having a complicated structure, and a DC light component increases by the scattered light. As a result, errors caused by the above phenomena are also added to further increase the errors. Also, errors caused by individual differences cannot be inevitably avoided, either.
The main reason why the problems for obtaining the absorptive constituent and an absorption coefficient in a scattering medium are complicated lies in that it is difficult to measure influences of the scattering and absorption coefficients separately, because the waveform of the scattered light output signal corresponding to the incident light pulse is deformed by scattering and absorption in the scattering medium, i.e., by the scattering and absorption coefficients. In other words, in the method of measuring the optical density, the optical density by its definition equalizes the scattering coefficient with the absorption coefficient as equivalent parameters. It is essentially difficult to separate the influences of the scattering and absorption coefficients and accurately obtain the influence of the absorption coefficient.
Sevick and Chance.sup.8) calculated the average optical path length of detected output light components from the barycenter, i.e., the average delay time of the waveform of an output signal and confirm dependency of the average optical path length on the absorption coefficient. They also attempt to measure absorptive constituents localized inside the scattering medium from a change in average optical path length.sup.8). According to their experimental result, the average optical path length apparently depends on absorption. This indicates that the method.sup.5) of Tamura et al. cannot measure the internal absorptive constituents accurately because the optical path length is assumed to be constant. The method of Sevick and Chance explicitly indicates that the concept of the average optical path length depending on absorption is introduced to allow measurement of absorption information in the scattering medium. However, the above average delay time can be obtained after the output signal waveform becomes apparent as a whole. For this reason, measurement of the average delay time must be performed until the output light signal having a long, gradually attenuated tail is sufficiently attenuated, thereby prolonging the measurement time. Since the output light signal is obtained by time-resolved measurement, the improvement of measurement precision of the average optical path length to improve measurement precision as a function of time undesirably causes a decrease in S/N ratio. Therefore, calculation precision of the average delay time, i.e., the barycenter has a limitation. Signal processing for obtaining the barycenter is complicated, and an apparatus for performing time-resolved measurement is generally complicated and bulky, resulting in an impractical application.
In contrast to the above prior arts, Gratton et al. propose a method.sup.9) utilizing light modulated with a sinusoidal wave in imaging of the interior of a scattering medium. This method utilizes coherent propagation of a wave having a modulated frequency component in the scattering medium, as will be described in detail with reference to the operational principle of the present invention. According to their report.sup.9), although a coherent wave propagating in the scattering medium is confirmed in their experiment, optical parameters of an actual sample do not match the theoretically calculated values. This study is still in the stage of fundamental study. Detailed findings and means for a method of obtaining absorption and scattering coefficients, a method of measuring a change in concentration of the absorptive constituents as a function of time, a method of imaging the interior of the scattering medium, and a method of obtaining a tomogram are not yet obtained.
Chance proposed a method and apparatus for determining the concentration of an absorptive constituent in a scattering medium utilizing modulated light in 1989 prior to the report of Gratton et al., and U.S. Pat. No. 4,972,331.sup.10) of this method was issued to Chance in 1990. According to his patent, an output signal upon incidence of modulated light on the scattering medium is detected and compared with a reference waveform (e.g., an incident light waveform) to determine a quantitatively measurable parameter, and the concentration of the absorptive constituent is quantitatively measured. In this case, a phase difference quantitatively measured by the method disclosed in the Chance's patent is equivalent to the optical path length, i.e., a distance up to the barycenter of the waveform obtained by the time-resolved measurement method.
This patent also discloses a method and apparatus utilizing the principle of dual-wavelength spectroscopy, i.e., a method and apparatus for alternately switching modulated light components having different wavelengths. According to Chance's patent, however, no practical method except that logarithmic conversion of the phase difference is proportional to the concentration of the absorptive constituent or the absorption coefficient is described about a relationship between optical parameters (e.g., the scattering coefficient of the scattering constituent in the scattering medium, the absorption coefficient of the absorptive constituent thereof, and the concentrations of the scattering and absorptive constituents) and the determined parameters (time, frequency, and phase). According to the analysis, examinations, and experimental results of the present inventor, to be described in detail later, however, the logarithmic conversion of the phase difference is not proportional to the concentration of the absorptive constituent or the absorption coefficient.
Judging form the above description, it is essentially impossible for the description of the Chance's patent to quantitatively measure the absorption coefficient of the absorptive constituent and its concentration.
The present invention does not utilize the relationship described by Chance. Since the present invention does not utilize the absorbance optical density method, the optical path length is not utilized.
In Chance's patent, any specific region through which light used for measurement pass through the scattering medium is not taken into consideration. That is, the average value of light components passing through the entire area of the scattering medium is taken into consideration. For this reason, measurement of absorptive constituents localized inside the scattering medium is not examined, as a matter of course.
Therefor, according to chance's patent, it is also impossible to measure the spatial distribution of the absorptive constituent which is inevitable in imaging and measurement of the interior of the scattering medium. In conclusion, according to Chance's patent, it is impossible to quantitatively measure the absorption coefficient and concentration of the absorptive constituent of a specific portion in the scattering medium, measure them with a change in time, and measure the spatial distribution of the absorptive constituent at all. In addition, it is also impossible to image the above constituents and form a tomogram, either.
In recent years, Sevick and Chance.sup.11) have made experiments to systematically examine and analyze the parameters obtained in the time-resolved measurement method and a method (they call this method a frequency-resolved measurement method) utilizing the modulated light, and have discussed the relationship between these parameters, including analysis results obtained by other researchers to verify their analysis results.sup.11). Most of the major conventional methods for measuring absorption information in the scattering medium are examined in this report, which is very convenient for us.
This report mainly describes detailed conventional applications of the time-resolved measurement method. The following method is described in detail. That is, a method to obtain parameters such as an average optical path length and an absorption coefficient from an output light signal obtained by the time-resolved measurement. And then by using these parameters, the concentration and absorption coefficient of the absorptive constituent of the scattering medium, the degree of saturation of hemoglobin (concentration of oxyhemoglobins with respect to the total amount of oxyhemoglobins and reduced hemoglobins), and the like are obtained. In this method, the barycenter (i.e. average delay time) of the output light signal waveform is obtained and multiplied with a light speed in the scattering medium to obtain the average optical path length.
A relationship between the parameters obtained by the time-resolved and frequency-resolved measurement methods is also clarified. For example, when the modulation frequency is low, the phase difference obtained by the frequency-resolved measurement method is found to be proportional to the average optical path length obtained by the time-resolved measurement method. As described above, according to the report of Sevick and Chance, the detailed method of obtaining the absorption information such as the concentration and absorption coefficient of the absorptive constituent of the scattering medium, the degree of saturation of hemoglobins, and the like using the optical path length is disclosed.
This measurement method has a disadvantage in that information associated with absorption is obtained from the time-resolved waveform of the output light signal. As previously described, since the measurement parameter for obtaining the absorption coefficients is the average delay time, the measurement precision is not essentially improved. The signal processing is considerably complicated, the signal processing time is prolonged, and the resultant apparatus becomes considerably bulky.
Lakowicz et al..sup.12) has reported an attempt of utilizing a phase modulation technique developed to measure an attenuation curve of laser-excited fluorescence in imaging of the scattering medium. This is a simple imaging technique. No consideration is made on quantitative measurement of the absorption coefficient and concentration of the absorptive constituent.
It is an object of the present invention to provide an apparatus for measuring absorption information in a scattering medium, capable of greatly improve the limitations of the method.sup.10) proposed by Chance and the method.sup.11) reported by Sevick and Chance, obtaining an image or tomogram representing the distribution of the absorptive constituent in the scattering medium, and quantitatively measuring the absorptive constituents in the image and tomogram, and a method therefor.
This object can be achieved by introduction of the concept of a photon density wave propagating in a scattering medium, a new finding of a relationship between quantitatively measurable parameters such as time, frequency, phase, and amplitude with respect to the photon density wave, and optical parameters such as the scattering coefficient of a scattering constituent in the scattering medium, the absorption coefficient of an absorptive constituent therein, and their concentrations, and a new and improved method of eliminating the influences of scattering from the measured data described above to accurately measure only the influence of absorption and/or perform signal processing.
Part of the basic principle utilized in the present invention is excluded from the examination and analysis range in A1.2 (pp. 348) of the report.sup.11) of Sevick and Chance because this method makes it impossible to perform measurement due to an excessively low S/N ratio.